The A/Alaska/77 (H3N2) ca reassortant was satisfactorily attenuated, genetically stable, and non-transmissible in seronegative adults. Its human infectious dose 50 was less than 10 to the 5.7 TCID50, however, it was not possible to infect more than 75% of volunteers when 10-100 fold more virus was given. Refractoriness of a subset of volunteers to a large dose of virus appeared to be mediated by immune factors. Individuals who were infected with 10-100 HID50 of virus lacked detectable nasal wash IgA antibody (1:2) to hemagglutinin, whereas refractory volunteers has a pre-existing antibody titer of 1:8 or greater. Another ca reassortant, the A/Cal/78 (H1N2) ca reassortant, was also attenuated at a dose of 10 to the 7.0 TCID50. Thus, transfer of all six internal genes from the ca donor strain A/AA/6/60 appears to reproducibly attenuate influenza A virus for adults.